Multi-omics analysis of the bladder and its sensitivity to inosine in a rat model of spinal cord injury

This study investigates the molecular changes in the bladder following spinal cord injury (SCI) in rats and the impact of inosine treatment using a multi-omics approach. We discovered the activation of PARP (Poly(ADP-ribose) polymerase) in response to SCI, a previously unrecognized phenomenon, and its attenuation with inosine treatment. SCI triggered significant DNA damage and oxidative stress pathways, whereas inosine treatment prevents DNA damage and inhibits PARP activation, offering a potential therapeutic avenue. The integrated analysis of transcriptomics and proteomics data revealed concordant regulation of multiple pathways following SCI, including EIF2 signaling and NRF2-mediated oxidative stress response, which are ameliorated by inosine treatment. These findings have relevance to human neurogenic bladder pathobiology. Pathway inhibition by inosine in the setting of SCI suggests its potential for neuroprotection in the bladder. Despite limitations, such as the focus on male rats and a lack of proteomics data from separated detrusor and mucosa, this study provides valuable insights into the molecular mechanisms underlying bladder dysfunction following SCI. It also suggests the repurposing of FDA-approved PARP inhibitors for the treatment of bladder dysfunction following spinal injury.